Hydrogen gas clearance is a recently developed method of measuring gastric mucosal blood flow (MBF). With a number of improvements in the technique, we have been able to reduce the concentration of the inhaled hydrogen gas from 100% to 3% while maintaining the sensitivity of this method. This modification avoids the potential risks of inflammability and explosiveness of using 100% H2 gas and makes this technique potentially an ideal method for measuring gastric MBF in experimental animals, as well as human subjects. In addition, this method also has the potential for determination of MBF of the duodenum, small intestine and colon; either through an endoscope or at the time of abdominal surgery. However, the validity and limitations of this method should be further evaluated and the technique must be refined before it can be accurately and reliably used clinically. It is the intent of this application to fill these gaps between our current knowledge of this technique and its readiness for clinical use by achieving the following specific goals. First, we propose to further evaluate the validity and limitations of this technique in measuring gastric MBF under various experimental conditions such as secretory stimulation and inhibition, and the presence of mucosal injury. Secondly, we will evaluate its accuracy in measuring duodenal, intestinal and colonic MBF. Lastly, we will attempt to overcome some of the technical difficulties associated with its use through and endoscope. The first goal will be accomplished by comparing gastric MBF as measured by this modified H2 gas clearance with that as determined by microspheres under these various conditions in dogs. Duodenal, intestinal and colonic MBF of the dogs as determined by H2 gas clearance will be correlated with those as determined by radioactive microspheres and 85Kr-elimination technique. In order to make measurements through an endoscope, the platinum electrode will be redesigned and reduced in size for its passage through a scope biopsy channel. The lengthening and reduction in size of the platinum electrode should not reduce its sensitivity to detect hydrogen gas in the mucosa. Its accurary will be validated against measurements currently made through a gastrotomy or enterotomy. Once these goals are accomplished, this modified technique of H2 gas clearance should be ready for its clinical use during endoscopic or operative procedures. This will allow us to pursue our long-term objective, that is to understand the role of MBF in the physiology and pathophysiology of the gastrointestinal trat by obtaining quantitative measurements of MBF in human subjects.